Is there any info on how the Tumor Mutational Burden is measured for the final dataset? I.e. is it from WGS, WES, or a targeted panel? And how is it calculated? Thanks!
Created by mclaurt Thanks @JosephSzustakowski !!
-Tyler @mclaurt - correct, these are the samples and data described in the NEJM paper referenced above.
-- Joe Just following up,
Is it safe to assume the data was generated according to the protocol I pasted above? Are these the exact same samples from the paper? Just making sure a different capture kit wasn't used to calculate TMB for the final DREAM challenge data set. Thank you, Mike. Very good to know.
One more question: the WES data itself for the challenge was generated according to the protocol in the NEJM article's supplementary appendix?
From the appendix:
"""
Whole exome capture and sequencing
Genomic DNA (150 ng) was used for library preparation using the Agilent SureSelectXT reagent
kit (Agilent Technologies, Santa Clara, USA) with the on-bead modifications of Fisher et al,
2011.1 A total of 500 ng of enriched library was used in the hybridization and captured with the
SureSelect All Exon v5 (Agilent Technologies, Santa Clara, USA) bait. Following hybridization,
the captured libraries were purified according to the manufacturer's recommendations and
amplified by polymerase chain reaction (11 cycles). Normalized libraries were pooled and DNA
was sequenced on the Illumina HiSeq 2500 using 2 x 100-bp paired-end reads; an average of 84
million reads were sequenced per tumor sample (average 84.6 x the mean tumor target
coverage), and an average of 89 million reads were sequenced per germline sample (average 93 x
the mean germline target coverage)
"""
-Tyler Dear @mclaurt
Thanks for participating in this Challenge. TMB was calculated in the same manner as in the [NEJM article *First-Line Nivolumab in Stage IV or Recurrent Non?Small-Cell Lung Cancer*](https://www.nejm.org/doi/10.1056/NEJMoa1613493?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub++0pubmed). Specifically , "The tumor-mutation burden, which was defined as the total number of somatic missense mutations present in a baseline tumor sample, was determined in patients with tumor and blood samples sufficient for whole-exome sequencing."
Kind Regards,
Mike
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